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Bacteria and viruses and clinical outcomes of asthma-bronchiectasis overlap syndrome: A cohort study 细菌和病毒与哮喘-支气管扩张重叠综合征的临床结果:一项队列研究
IF 4.4 2区 医学 Q2 ALLERGY Pub Date : 2024-01-11 DOI: 10.1002/clt2.12331
Xiao-xian Zhang, Jia-hui He, Cui-xia Pan, Zhen-feng He, Hui-min Li, Zhen-hong Lin, Xiao-fen Zhang, Lai-jian Cen, Ri-lan Zhang, Ming-xin Shi, Wei-jie Guan

Background

Despite the high prevalence of co-existing bronchiectasis and asthma (asthma-bronchiectasis overlap syndrome [ABOS]), little is known regarding the dominant pathogens and clinical correlates.

Objective

To investigate the bacteria and viruses which differentially dominate in ABOS (including its subtypes) compared with bronchiectasis alone, and determine their relevance with bronchiectasis severity and exacerbations.

Methods

This was a prospective observational cohort study conducted between March 2017 and August 2023. We included 81 patients with ABOS and 107 patients with bronchiectasis alone. At steady-state baseline, patients underwent comprehensive assessments and sputum collection for bacterial culture and viral detection (quantitative polymerase-chain-reaction). Patients were followed-up to record exacerbation and spirometry.

Results

Patients with ABOS had significantly higher symptom burden and exacerbation frequency than those with bronchiectasis alone. Despite similar pathogen spectrum, the rate of bacteria–virus co-detection increased less substantially at acute exacerbations (AE) onset than at steady-state compared with bronchiectasis alone. Pathogenic bacteria (particularly Pseudomonas aeruginosa) were detected fairly common (exceeding 50%) in ABOS and were associated with greater severity of bronchiectasis when stable and conferred greater exacerbation risks at follow-up. Viral but not bacterial compositions changed substantially at AE onset compared with clinical stability. Higher blood eosinophil count, moderate-to-severe bronchiectasis and non-atopy were associated with higher odds of bacterial, but not viral, detection (all p < 0.05).

Conclusion

Detection of bacteria or virus is associated with bronchiectasis severity or clinical outcomes in ABOS. This highlights the importance of integrating sputum microbial assessment for ascertaining the dominant pathophysiology (atopy vs. infection) and longitudinal trajectory prediction in ABOS.

背景 尽管支气管扩张和哮喘(哮喘-支气管扩张重叠综合征 [ABOS])并存的发病率很高,但人们对主要病原体和临床相关性知之甚少。 目的 研究与单纯支气管扩张相比,在 ABOS(包括其亚型)中占主导地位的细菌和病毒,并确定它们与支气管扩张严重程度和病情加重的相关性。 方法 这是一项前瞻性观察性队列研究,研究时间为 2017 年 3 月至 2023 年 8 月。我们纳入了 81 名 ABOS 患者和 107 名单纯支气管扩张症患者。在稳态基线时,患者接受综合评估,并采集痰液进行细菌培养和病毒检测(定量聚合酶链式反应)。对患者进行随访,记录病情加重情况和肺活量。 结果 ABOS 患者的症状负担和恶化频率明显高于单纯支气管扩张症患者。尽管病原体谱相似,但与单纯性支气管扩张症相比,细菌-病毒共同检测率在急性加重(AE)开始时的增加幅度小于稳定期。在 ABOS 中,病原菌(尤其是铜绿假单胞菌)的检出率相当高(超过 50%),在病情稳定时与支气管扩张的严重程度相关,在随访时会带来更大的病情加重风险。与临床稳定期相比,AE 发病时病毒(而非细菌)成分发生了重大变化。较高的血液嗜酸性粒细胞计数、中度至重度支气管扩张和无炎症与较高的细菌检测几率相关,但与病毒检测几率无关(所有 p < 0.05)。 结论 细菌或病毒的检测与 ABOS 的支气管扩张严重程度或临床结果有关。这凸显了综合痰微生物评估对确定主要病理生理学(特异性与感染)和纵向预测 ABOS 病变轨迹的重要性。
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引用次数: 0
CRUSE®—An innovative mobile application for patient monitoring and management in chronic spontaneous urticaria CRUSE®-用于慢性自发性荨麻疹患者监测和管理的创新型移动应用程序
IF 4.4 2区 医学 Q2 ALLERGY Pub Date : 2024-01-03 DOI: 10.1002/clt2.12328
Sophia Neisinger, Bernardo Sousa Pinto, Aiste Ramanauskaite, Jean Bousquet, Karsten Weller, Martin Metz, Markus Magerl, Emek Kocatürk, Ivan Cherrez-Ojeda, Ana M. Gimenez-Arnau, Claudio Alberto S. Parisi, Sabine Altrichter, Luis Felipe Ensina, Laurence Bouillet, Riccardo Asero, Margarida Gonçalo, Carole Guillet, Krzysztof Rutkowski, Jonathan A. Bernstein, Hannah Hardin, Kiran Godse, Zenon Brzoza, Jose Ignacio Larco Sousa, Simon Francis Thomsen, Martijn van Doorn, Michihiro Hide, Young-Min Ye, Staffan Vanderse, Lāsma Lapiņa, Jonny Peter, Zuotao Zhao, Lianyi Han, Iman Nasr, Heike Rockmann-Helmbach, Jennifer Astrup Sørensen, Rabia Öztaş Kara, Natalja Kurjāne, Andrii I. Kurchenko, Igor Kaidashev, Vladyslav Tsaryk, Roman Stepanenko, Marcus Maurer

Background

Chronic spontaneous urticaria (CSU) is unpredictable and can severely impair patients' quality of life. Patients with CSU need a convenient, user-friendly platform to complete patient-reported outcome measures (PROMs) on their mobile devices. CRUSE®, the Chronic Urticaria Self Evaluation app, aims to address this unmet need.

Methods

CRUSE® was developed by an international steering committee of urticaria specialists. Priorities for the app based on recent findings in CSU were defined to allow patients to track and record their symptoms and medication use over time and send photographs. The CRUSE® app collects patient data such as age, sex, disease onset, triggers, medication, and CSU characteristics that can be sent securely to physicians, providing real-time insights. Additionally, CRUSE® contains PROMs to assess disease activity and control, which are individualised to patient profiles and clinical manifestations.

Results

CRUSE® was launched in Germany in March 2022 and is now available for free in 17 countries. It is adapted to the local language and displays a country-specific list of available urticaria medications. English and Ukrainian versions are available worldwide. From July 2022 to June 2023, 25,710 observations were documented by 2540 users; 72.7% were females, with a mean age of 39.6 years. At baseline, 93.7% and 51.3% of users had wheals and angioedema, respectively. Second-generation antihistamines were used in 74.0% of days.

Conclusions

The initial data from CRUSE® show the wide use and utility of effectively tracking patients' disease activity and control, paving the way for personalised CSU management.

背景 慢性自发性荨麻疹(CSU)难以预测,会严重影响患者的生活质量。慢性自发性荨麻疹患者需要一个方便、用户友好的平台,在移动设备上完成患者报告的结果测量(PROMs)。慢性荨麻疹自我评估应用程序 CRUSE® 旨在满足这一尚未满足的需求。 方法 CRUSE® 由荨麻疹专家组成的国际指导委员会开发。根据最近对慢性荨麻疹的研究结果,确定了该应用程序的优先事项,即允许患者跟踪和记录自己的症状和用药情况,并发送照片。CRUSE® 应用程序收集患者数据,如年龄、性别、发病时间、诱发因素、用药情况和 CSU 特征,这些数据可安全地发送给医生,提供实时见解。此外,CRUSE® 还包含用于评估疾病活动和控制情况的 PROMs,可根据患者情况和临床表现进行个性化设置。 结果 CRUSE® 于 2022 年 3 月在德国推出,目前在 17 个国家免费提供。它根据当地语言进行了调整,并显示针对特定国家的可用荨麻疹药物列表。英语版和乌克兰语版已在全球推出。从 2022 年 7 月到 2023 年 6 月,共有 2540 名用户记录了 25710 次观察结果;其中 72.7% 为女性,平均年龄为 39.6 岁。基线时,分别有 93.7% 和 51.3% 的使用者出现喘息和血管性水肿。74.0%的患者使用了第二代抗组胺药。 结论 CRUSE® 的初步数据表明,有效跟踪患者的疾病活动和控制情况具有广泛的用途和效用,为个性化 CSU 管理铺平了道路。
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引用次数: 0
Clinical characteristics of allergic bronchopulmonary mycosis caused by Schizophyllum commune 五味子引起的过敏性支气管肺霉菌病的临床特征
IF 4.4 2区 医学 Q2 ALLERGY Pub Date : 2023-12-31 DOI: 10.1002/clt2.12327
Tsuyoshi Oguma, Takashi Ishiguro, Katsuhiko Kamei, Jun Tanaka, Junko Suzuki, Akira Hebisawa, Yasushi Obase, Hiroshi Mukae, Takae Tanosaki, Shiho Furusho, Koji Kurokawa, Kentaro Watai, Hiroto Matsuse, Norihiro Harada, Ai Nakamura, Takuo Shibayama, Rie Baba, Kentaro Fukunaga, Hisako Matsumoto, Hisano Ohba, Susumu Sakamoto, Shinko Suzuki, Shintetsu Tanaka, Takahiro Yamada, Akira Yamasaki, Yuma Fukutomi, Yoshiki Shiraishi, Takahito Toyotome, Koichi Fukunaga, Terufumi Shimoda, Satoshi Konno, Masami Taniguchi, Katsuyoshi Tomomatsu, Naoki Okada, Koichiro Asano, Japan ABPM Research Program

Background

Allergic bronchopulmonary mycosis (ABPM) is an allergic disease caused by type I and type III hypersensitivity to environmental fungi. Schizophyllum commune, a basidiomycete fungus, is one of the most common fungi that causes non-Aspergillus ABPM.

Objective

Herein, we attempted to clarify the clinical characteristics of ABPM caused by S. commune (ABPM-Sc) compared with those of allergic bronchopulmonary aspergillosis (ABPA).

Methods

Patients with ABPM-Sc or ABPA were recruited from a nationwide survey in Japan, a multicenter cohort, and a fungal database at the Medical Mycology Research Center of Chiba University. The definition of culture-positive ABPM-Sc/ABPA is as follows: (1) fulfills five or more of the 10 diagnostic criteria for ABPM proposed by Asano et al., and (2) positive culture of S. commune/Aspergillus spp. in sputum, bronchial lavage fluid, or mucus plugs in the bronchi.

Results

Thirty patients with ABPM-Sc and 46 with ABPA were recruited. Patients with ABPM-Sc exhibited less severe asthma and presented with better pulmonary function than those with ABPA (p = 0.008–0.03). Central bronchiectasis was more common in ABPM-Sc than that in ABPA, whereas peripheral lung lesions, including infiltrates/ground-glass opacities or fibrotic/cystic changes, were less frequent in ABPM-Sc. Aspergillus fumigatus-specific immunoglobulin (Ig)E was negative in 10 patients (34%) with ABPM-Sc, who demonstrated a lower prevalence of asthma and levels of total serum IgE than those with ABPM-Sc positive for A. fumigatus-specific IgE or ABPA.

Conclusions

Clinical characteristics of ABPM-Sc, especially those negative for A. fumigatus-specific IgE, differed from those of ABPA.

过敏性支气管肺霉菌病(ABPM)是一种由对环境真菌的 I 型和 III 型过敏引起的过敏性疾病。基生真菌 Schizophyllum commune 是引起非曲霉性支气管肺霉病的最常见真菌之一。
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引用次数: 0
Assessment of the effectiveness of the peptide inhibitor homologous to the transforming growth factor β cytokine blocking the TGFβRI/TGFβRII receptor complex—pilot study 评估与转化生长因子β细胞因子同源的多肽抑制剂阻断 TGFβRI/TGFβRII 受体复合体的有效性--试验研究
IF 4.4 2区 医学 Q2 ALLERGY Pub Date : 2023-12-31 DOI: 10.1002/clt2.12320
Marynowski Mateusz, Karbownik Michał Seweryn, Szemraj Janusz, Kuna Piotr, Michał Gabriel Panek

Background

A key player in the fibrotic process is the transforming growth factor β (TGF-β) which enhances extracellular matrix production by increasing the transcription of matrix proteins. The cytokine TGF-β first binds to the TGFβRII receptor (dimer), resulting in the recruitment of the TGFβRI receptor (dimer). The complex thus formed leads to the phosphorylation of the kinase domain of TGFβRI, which in turn results in activation of the Smad pathway. This is therefore a targeted pathway for research into the application of peptide inhibitors in blocking the TGF-β-Smad signaling pathway. The aim of this study was to design a peptide inhibitor (homologous to the cytokine TGF-β) which, after binding to the TGFβRI/TGFβRII receptor, would block the cytokine binding and thus prevent the formation of an activating complex.

Methods

Preliminary work on the design and synthesis of inhibitors for TGFβRI/TGFβRII has allowed us to identify and describe five key regions of the TGF-β—TGFβRI/TGFβRII interface. The following five peptide inhibitors were synthesized for Region 1: 1.1 ALDAAYCFR, 1.2 LDAAYCFRN, 1.3 DAAYCFRNV, 1.4 AAYCFRNVQ, 1.5 AYCFRNVQD. The expression of the SEAP reporter gene, Smad2, Smad3, Smad4, and JNK1 gene was measured using quantitative real-time polymerase chain reaction.

Results

For Region 1 peptide inhibitors tested for TGFβRI/TGFβRII, reduced SEAP (reporter gene) expression was observed in cells of the MFB-F11 line, which suggests inhibited the formation of cytokine-receptor complexes.

Conclusions

For IP1_2, 1_3 and 1_5 Region 1 peptides tested for TGFβRI/TGFβRII, reduced cytokine-receptor signal by adding newly designed inhibitors. The study revealed an impact of these peptide inhibitors on the reduction of mRNA expression of Smad2, Smad3, Smad4 and JNK1 genes.

在纤维化过程中起关键作用的是转化生长因子β(TGF-β),它通过增加基质蛋白的转录来促进细胞外基质的生成。细胞因子 TGF-β 首先与 TGFβRII 受体(二聚体)结合,从而招募 TGFβRI 受体(二聚体)。由此形成的复合物导致 TGFβRI 的激酶结构域磷酸化,进而激活 Smad 通路。因此,这是研究多肽抑制剂在阻断 TGF-β-Smad 信号通路中应用的一个目标通路。本研究的目的是设计一种多肽抑制剂(与细胞因子 TGF-β 同源),它与 TGFβRI/TGFβRII 受体结合后,会阻断细胞因子的结合,从而阻止活化复合物的形成。
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引用次数: 0
Tolerance to heated egg in egg allergy: Explanations and implications for prevention and treatment 鸡蛋过敏症患者对加热鸡蛋的耐受性:对预防和治疗的解释和影响
IF 4.4 2区 医学 Q2 ALLERGY Pub Date : 2023-12-21 DOI: 10.1002/clt2.12312
Audrey Leau, Sandra Denery-Papini, Marie Bodinier, Wieneke Dijk

Hen's egg allergy is the second most frequent food allergy found in children. Allergic symptoms can be caused by raw or heated egg, but a majority of egg-allergic children can tolerate hard-boiled or baked egg. Understanding the reasons for the tolerance towards heated egg provides clues about the molecular mechanisms involved in egg allergy, and the differential allergenicity of heated and baked egg might be exploited to prevent or treat egg allergy. In this review, we therefore discuss (i) why some patients are able to tolerate heated egg; by highlighting the structural changes of egg white (EW) proteins upon heating and their impact on immunoreactivity, as well as patient characteristics, and (ii) to what extent heated or baked EW might be useful for primary prevention strategies or oral immunotherapy. We describe that the level of immunoreactivity towards EW helps to discriminate patients tolerant or reactive to heated or baked egg. Furthermore, the use of heated or baked egg seems effective in primary prevention strategies and might limit adverse reactions. Oral immunotherapy is a promising treatment strategy, but it can sometimes cause significant adverse events. The use of heated or baked egg might limit these, but current literature is insufficient to conclude about its efficacy.

摘要 母鸡蛋过敏是儿童中第二常见的食物过敏症。生鸡蛋或加热鸡蛋都可能引起过敏症状,但大多数鸡蛋过敏儿童都能耐受煮熟或烤熟的鸡蛋。了解对加热鸡蛋耐受的原因可为鸡蛋过敏的分子机制提供线索,加热鸡蛋和烤鸡蛋的不同过敏性可用于预防或治疗鸡蛋过敏。因此,在这篇综述中,我们将讨论:(i) 为什么有些患者能够耐受加热鸡蛋;通过强调蛋白 (EW) 蛋白在加热后的结构变化及其对免疫反应性的影响,以及患者的特征;(ii) 加热或烘焙 EW 在多大程度上可用于初级预防策略或口服免疫疗法。我们发现,对 EW 的免疫反应水平有助于区分患者对加热或烘烤鸡蛋的耐受性或反应性。此外,在一级预防策略中使用加热或烘烤的鸡蛋似乎很有效,并可限制不良反应。口服免疫疗法是一种很有前景的治疗策略,但有时会引起严重的不良反应。使用加热或烘烤的鸡蛋可能会限制这些不良反应,但目前的文献还不足以对其疗效做出结论。
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引用次数: 0
Food allergy: What are people looking for? An infodemiology study 食物过敏:人们在寻找什么?信息学研究
IF 4.4 2区 医学 Q2 ALLERGY Pub Date : 2023-12-20 DOI: 10.1002/clt2.12322
Karla Robles-Velasco, Matias Panchana-Lascano, Flavio Veintemilla-Burgos, Romina Hinostroza, Jonathan A. Bernstein, Ivan Cherrez-Ojeda
<p>Food allergy (FA), an immunoglobulin E (IgE) reaction, is rising steadily over time.<span><sup>1</sup></span> FA is present in 10% of the population, varying according to region.<span><sup>2</sup></span> Google's search engine has become a significant source of medical information; however, this information varies in quality. Google Trends (GTr) is a free online service that gives users access to current and historical data on Google searches from 2004 up to the present.<span><sup>3</sup></span></p><p>This study aims to assess the public interest and information-seeking behavior regarding food allergies over a specified period. We conducted several searches on GTr (http://trends.google.com) on April 1st, 2023. The data was downloaded and compiled at once across 10 countries from January 1, 2012, to December 31, 2022. Based on a literature review indicating high prevalence in various countries three different types of food were selected as the primary allergens.<span><sup>4</sup></span> These allergens were used as search topics in GTr, and include: “milk allergy,” “peanut allergy,” and “shellfish allergy.” The countries were selected using GTr performing a search for “Food allergy” as a topic with the "worldwide" category, we analyzed the countries with a relative search volume (RSV) score higher than 50. Ten countries were included: Australia, Canada, Finland, Hungary, Ireland, Netherlands, New Zealand, Philippines, Singapore, and the USA. Ten different searches were performed, one search for each of the 10 countries. Each search containing the three allergens, and done under the category “Health” in GTr. RSV is a value that expresses the relation between a specific search concerning the overall searches on Google at a specific time among other modifiable variables. RSV ranges between 100 and 0 in descending order, the former being a high popularity and the latter a low one. For this study, search volume trends and interest over time were developed using Statistical Package for Social Science (version 21.0; SPSS).</p><p>Over the years, there has been a noticeable growth in people's interest in searching about “food allergy” as a topic of search, as evidenced by increased Google search trends from 2012 to 2022 in the 10 countries examined. Although the interest in peanut allergy has been relatively low in the last decade, in the last 2 years there has been a prominent increase in searches in Australia, the USA, Finland, the Netherlands, and New Zealand. On the other hand, there was a decreasing interest in Canada, Hungary, Ireland, and the Philippines. Milk allergy was the most searched topic in 6 out of 10 countries of interest, with a sharp spike since 2021 in Canada, the USA, and Australia. In contrast, “shellfish allergy” showed the lowest RSV, being only searched mainly in the Philippines and Singapore (Figure 1).</p><p>The related queries with the most interest were different terms and definitions for allergy, such as “allergy,” “allergi
食物过敏(FA)是一种免疫球蛋白 E(IgE)反应,其发病率随着时间的推移而持续上升。2 谷歌搜索引擎已成为医疗信息的重要来源,但这些信息的质量参差不齐。谷歌趋势(GTr)是一项免费的在线服务,用户可以通过它获取从 2004 年至今谷歌搜索的当前和历史数据。我们于 2023 年 4 月 1 日在 GTr (http://trends.google.com) 上进行了多次搜索。从 2012 年 1 月 1 日至 2022 年 12 月 31 日,我们一次性下载并汇编了 10 个国家的数据。4 这些过敏原被用作 GTr 的搜索主题,包括4 这些过敏原被用作 GTr 的搜索主题,包括:"牛奶过敏"、"花生过敏 "和 "贝类过敏"。通过 GTr 以 "全球 "类别搜索 "食物过敏 "作为主题来选择国家,我们分析了相对搜索量(RSV)得分高于 50 的国家。其中包括 10 个国家:澳大利亚、加拿大、芬兰、匈牙利、爱尔兰、荷兰、新西兰、菲律宾、新加坡和美国。共进行了 10 次不同的搜索,10 个国家各一次。每个搜索都包含三种过敏原,并且是在 GTr 的 "健康 "类别下进行的。 RSV 是一个值,表示特定搜索与特定时间内 Google 上其他可修改变量的总体搜索之间的关系。RSV 值从高到低依次在 100 和 0 之间,前者表示受欢迎程度高,后者表示受欢迎程度低。在本研究中,使用社会科学统计软件包(21.0 版;SPSS)对搜索量趋势和兴趣随时间的变化进行了分析。多年来,人们对 "食物过敏 "这一搜索主题的兴趣明显增加,这从 2012 年至 2022 年 10 个国家的谷歌搜索趋势增长中可见一斑。虽然在过去十年中,人们对花生过敏的兴趣相对较低,但在过去两年中,澳大利亚、美国、芬兰、荷兰和新西兰的搜索量显著增加。另一方面,加拿大、匈牙利、爱尔兰和菲律宾对花生过敏的兴趣却在下降。在 10 个相关国家中,牛奶过敏是 6 个国家中搜索次数最多的话题,其中加拿大、美国和澳大利亚的搜索次数自 2021 年以来急剧上升。相比之下,"贝类过敏 "显示出最低的 RSV,主要只在菲律宾和新加坡被搜索(图 1)。最感兴趣的相关查询是过敏的不同术语和定义,如 "过敏"、"过敏"、"食物过敏 "和 "花生过敏"。搜索次数最多的体征和症状包括 "皮疹"、"湿疹"、"荨麻疹 "和 "过敏性休克"。搜索体征和症状最多的国家是美国,过敏原是贝类。搜索与牛奶过敏有关的一些疾病的兴趣很高,包括 "乳糖不耐症"、"奶制品不耐症 "和 "乳糜泻"。查询诊断方法最多的国家是爱尔兰和匈牙利,查询内容包括 "食物过敏测试 "和 "食物不耐受测试"。"婴儿 "和 "学步期儿童 "是与年龄相关的搜索,在 10 个国家中,有 8 个国家将前者列入搜索量前五名。在菲律宾,"肾上腺素"、"免疫球蛋白"、"西替利嗪 "和 "抗组胺药 "被确定为 RSV 最高的治疗查询(表 1)。在医学领域,一些例子包括预测过敏性鼻炎的流行病学特征、确定哮喘住院与普通感冒之间的相关性、揭示鼻息肉的关注高峰等。5-7 在 10 个选定国家中,有 6 个国家在 2021 年对牛奶过敏的关注高峰可能与英国的一项研究结果有关8 ,该研究表明,牛奶过敏可能是四分之三的新生儿在出生后第一年的某个阶段出现两种或两种以上过敏症状的根源。造成这种趋势性现象的另一个可能原因是 2022 年 5 月美国因阿博特婴儿配方奶粉产品受污染而导致的婴儿住院和死亡事件。9 全世界贝类过敏的发病率在 0.2% 到 0.6% 之间,但这一数字在亚太地区要高得多。
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引用次数: 0
Clinical relevance of pre- and coseasonal sublingual immunotherapy with a 300 index of reactivity 5-grass SLIT tablet in allergic rhinoconjunctivitis 在过敏性鼻结膜炎中使用反应指数为 300 的 5-grass SLIT 片剂进行季节前和季节间舌下免疫疗法的临床意义
IF 4.4 2区 医学 Q2 ALLERGY Pub Date : 2023-12-18 DOI: 10.1002/clt2.12321
Oliver Pfaar, Ulrich Wahn, Giorgio Walter Canonica, Farah Bahbah, Philippe Devillier

Background

There is considerable interest in improving the scoring methods for evaluating the efficacy of allergen immunotherapy (AIT) and to show if this is associated with clinically meaningful results from the patient's perspective. We aimed to assess the efficacy and clinical relevance of a 300 index of reactivity (IR) 5-grass pollen sublingual immunotherapy (SLIT) tablet in children, adolescents and adults with moderate to severe grass-induced allergic rhinoconjunctivitis (ARC) with or without controlled asthma using the combined symptom and medication score CSMS0-36.

Methods

The data of the European population that participated in 3 Phase III, international, randomized double-blind placebo-controlled clinical trials were analyzed post hoc.

Results

A total of 864 patients randomized to 300 IR 5-grass tablet or placebo were analyzed. Over the primary evaluation period, the difference in CSMS0-36 between the 300 IR and placebo groups was statistically significant (point estimates: −2.51, CI95% [−3.88; −1.14], p < 0.0001 in clinical trial1; −2.31, CI95% [−3.39; −1.23], p < 0.0001 in CT2; and −2.31, CI95% [−3.58; −1.03], p = 0.0004 in CT3). The relative differences between the 300 IR 5-grass tablet and placebo were −29.7%, −33.8%, and −26.3%, respectively. The results based on CSMS0-36 were consistent with those obtained with the primary endpoints of the trials and support the consideration of the 2-point threshold of the CSMS0-36 for clinical relevance of AIT.

Conclusion

Post hoc analysis of 3 CTs with the 300 IR 5-grass SLIT tablet confirmed its significant and clinically relevant effect in the European population with grass pollen-induced ARC with or without controlled asthma.

背景 人们对改进过敏原免疫疗法(AIT)疗效评估的评分方法以及从患者的角度看这是否与有临床意义的结果相关联非常感兴趣。我们的目的是利用症状和药物综合评分 CSMS0-36,评估 300 反应指数(IR)5-禾本科花粉舌下免疫疗法(SLIT)片剂对患有中度至重度禾本科花粉引起的过敏性鼻结膜炎(ARC)并伴有或不伴有哮喘控制的儿童、青少年和成人的疗效和临床相关性。 方法 对参加 3 项 III 期国际随机双盲安慰剂对照临床试验的欧洲人群的数据进行了事后分析。 结果 共分析了 864 名随机服用 300 IR 5-草片或安慰剂的患者。在主要评估期间,300 IR 组和安慰剂组的 CSMS0-36 差异具有统计学意义(点估计值:-2.51,CI95:在临床试验1中为-2.51,CI95% [-3.88; -1.14], p < 0.0001;在临床试验2中为-2.31,CI95% [-3.39; -1.23], p < 0.0001;在临床试验3中为-2.31,CI95% [-3.58; -1.03], p = 0.0004)。300IR五味草片与安慰剂的相对差异分别为-29.7%、-33.8%和-26.3%。基于 CSMS0-36 的结果与试验主要终点的结果一致,并支持将 CSMS0-36 的 2 分阈值作为 AIT 临床相关性的考虑因素。 结论 对使用 300 IR 5-草酸 SLIT 片剂的 3 项 CT 进行的事后分析证实,该药物在欧洲草花粉诱发 ARC 并伴有或不伴有哮喘控制的人群中具有显著的临床相关性效果。
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引用次数: 0
Adrenaline auto injectors pharmacokinetic/pharmacodynamic studies and potential consequences for clinical practice 肾上腺素自动注射器药代动力学/药效学研究及对临床实践的潜在影响
IF 4.4 2区 医学 Q2 ALLERGY Pub Date : 2023-12-18 DOI: 10.1002/clt2.12323
Margitta Worm, Adam T. Fox, Magnus Wickman, Johannes Ring, Motohiro Ebisawa, Guillaume Pouessel, Pete Smith

Background

Anaphylaxis is a sudden multisystem allergic reaction which may result in a fatal outcome if not treated promptly. Guidelines worldwide suggest intramuscular adrenaline as the first-line treatment for anaphylaxis outside a perioperative reaction. Adrenaline autoinjectors (AAIs) are widely used self-administrable devices, especially in community settings. Different commercial AAIs have been authorized to be marketed in Europe. For an AAI to be efficacious, a rapid adrenaline delivery in patients, including those who are overweight or obese, resulting in an optimal cardiovascular (CV) response, is a key feature. AAIs are designed to achieve this requirement, which is reflected in their differing functional properties such as primary container selection, drug delivery mechanism (cartridge-or syringe-based), needle length, needle gauge, and adrenaline dose (150 μg, 300 μg, or 500 μg). However, the differences in functional properties across these devices may play a critical role in achieving these requirements as well as the differences in ergonomics in the handling of these devices.

The purpose of this review

Considering the dynamic pharmacokinetic/pharmacodynamic (PK/PD) profiles of different AAIs marketed in Europe and their effect on adrenaline delivery, the expert panel, also serving as author for this paper have carried out a detailed analysis of the PK/PD profiles of four AAIs, namely, Anapen, Emerade, EpiPen, and Jext, to delineate the adrenaline delivery and their subsequent physiological effects on the backdrop of device characteristics, dose strength, and the skin-to-muscle distances of the participants.

背景 过敏性休克是一种突发性多系统过敏反应,如不及时治疗可能会导致死亡。全球指南建议将肾上腺素肌肉注射作为围手术期反应之外的过敏性休克的一线治疗方法。肾上腺素自动注射器(AAI)是一种广泛使用的自行给药装置,尤其是在社区环境中。欧洲已授权销售不同的商用 AAI。自动肾上腺素注射器的一个关键特点是能快速为患者(包括超重或肥胖患者)注射肾上腺素,从而产生最佳的心血管(CV)反应。AAI 就是为实现这一要求而设计的,这反映在其不同的功能特性上,如主容器的选择、给药机制(盒式或注射器式)、针头长度、针头规格和肾上腺素剂量(150 微克、300 微克或 500 微克)。然而,这些设备在功能特性上的差异以及在操作上的人体工学差异可能会对实现这些要求起到至关重要的作用。 本综述的目的 考虑到在欧洲市场上销售的不同 AAI 的动态药代动力学/药效学(PK/PD)特征及其对肾上腺素给药的影响,同时也是本文作者的专家小组对四种 AAI(即 Anapen、Emerade、EpiPen 和 Jext)的 PK/PD 特征进行了详细分析,以根据设备特征、剂量强度和参与者的皮肤到肌肉的距离来描述肾上腺素的给药及其随后的生理效应。
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引用次数: 0
Comparative analysis of cysteine proteases reveals gene family evolution of the group 1 allergens in astigmatic mites 半胱氨酸蛋白酶的比较分析揭示了星螨第 1 组过敏原基因家族的进化过程
IF 4.4 2区 医学 Q2 ALLERGY Pub Date : 2023-12-15 DOI: 10.1002/clt2.12324
Ling Shi, Qing Xiong, Fu Kiu Ao, Tsz Yau Wan, Xiaojun Xiao, Xiaoyu Liu, Baoqing Sun, Anchalee Tungtrongchitr, Ting Fan Leung, Stephen Kwok Wing Tsui

Background

Astigmatic mites contain potent allergens that can trigger IgE-mediated immune responses, leading to allergic diseases such as asthma, allergic rhinitis and atopic dermatitis. In house dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae, group 1 allergens (Der p 1 and Der f 1), characterized as papain-like cysteine proteases, have been defined as the major allergens that have high prevalence and potency. Previous studies of mite group 1 allergens mainly focused on identification, comparison of sequence and structure, as well as the investigation of cross-reactivity. To achieve a comprehensive view of mite group 1 allergens, we performed a comparative genomic analysis of all the cysteine proteases in six astigmatic mite species to elucidate the evolutionary relationships of group 1 allergens.

Methods

Based on the high-quality and annotated genomes, all the cysteine proteases in six astigmatic mite species were identified by sequence homology search. The phylogenetic relationships, gene synteny and expression levels were revealed by bioinformatic tools. The allergenicity of recombinant cysteine proteases was evaluated by enzyme-linked immunosorbent assay.

Results

Tandem duplication was revealed as the major feature of cysteine protease gene evolution in astigmatic mites. The high IgE-binding capacity and the significant expression level of the cysteine protease DP_007902.01 suggested its potential as a novel group 1 allergen of D. pteronyssinus. In addition, gene decay events were identified in the skin-burrowing parasitic mite Sarcoptes scabiei.

Conclusion

This comprehensive analysis provided insights into the evolution of cysteine proteases, as well as the component-resolved diagnosis of mite allergies.

散光螨含有强效过敏原,可触发ige介导的免疫反应,导致过敏性疾病,如哮喘、过敏性鼻炎和特应性皮炎。在室内尘螨中,以木瓜蛋白酶样半胱氨酸蛋白酶为特征的1族过敏原(Der p1和Der f1)被认为是流行率和效力高的主要过敏原。以往对螨1族过敏原的研究主要集中在鉴定、序列结构比较、交叉反应性研究等方面。为了全面了解螨虫1族过敏原,我们对6种散光螨的所有半胱氨酸蛋白酶进行了比较基因组分析,以阐明1族过敏原的进化关系。方法基于高质量和注释的基因组,通过序列同源性检索对6种散光螨的所有半胱氨酸蛋白酶进行鉴定。利用生物信息学工具揭示了它们的系统发育关系、基因合群和表达水平。采用酶联免疫吸附法评价重组半胱氨酸蛋白酶的致敏性。结果发现串联重复是散光螨半胱氨酸蛋白酶基因进化的主要特征。半胱氨酸蛋白酶DP_007902.01具有高的ige结合能力和显著的表达水平,提示其可能是一种新的翼鸟鼻炎1组过敏原。此外,在皮肤穴居寄生螨疥螨中发现了基因衰变事件。结论该综合分析有助于了解半胱氨酸蛋白酶的进化,以及螨过敏的成分解析诊断。
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引用次数: 0
Cognitive, neuropsychiatric and neurological alterations in mastocytosis: A systematic review 肥大细胞增多症的认知、神经精神和神经系统改变:系统综述
IF 4.4 2区 医学 Q2 ALLERGY Pub Date : 2023-12-13 DOI: 10.1002/clt2.12319
Elena Sagües-Sesé, Natalia García-Casares, Ivan Álvarez-Twose

Background

Mastocytosis manifests with multisystemic symptoms, often involving the nervous system. Numerous cognitive, neuropsychiatric and neurological alterations have been reported in multiple observational studies.

Methods

We performed a qualitative systematic literature review of reported data consulting the electronic databases Medline, Scopus, Web of Science, Cochrane, and BASE until June 2023.

Results

We selected 24 studies in which the majority showed that a high proportion of mastocytosis patients suffer cognitive, neuropsychiatric and neurological alterations. The most common disorders and estimated ranges of frequency observed in adults were depression (68%–75%), anxiety, high stress or irritability (27%–54%), cognitive impairment (27%–39%, primarily affecting memory skills), and headaches (55%–69%). Attention challenges and learning difficulties were reported in children at a rate of 13%, while neurodevelopmental disorders occurred at rates of 8%–12%. Frequent white abnormalities in mastocytosis patients with concomitant psychocognitive symptoms have been reported although neuroimaging studies have been performed rarely in this population.

Conclusion

Further studies with more comprehensive and homogeneous evaluations and neuroimaging and histological analysis should be performed for a better understanding of these manifestations. An earlier detection and proper management of these symptoms could greatly improve the quality of life of these patients.

肥大细胞增多症表现为多系统症状,常累及神经系统。多项观察性研究报告了许多认知、神经精神和神经学方面的改变。
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引用次数: 0
期刊
Clinical and Translational Allergy
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